Most common cleaning methods for reusable medical devices and biomaterials rely on manual and automated washing, using brushes to dislodge soil in the presence of water and detergents, or organic solvents. However, the cleaning apparatus may compound the accumulation of residual soil by causing surface abrasion or grooving. Failure to successfully clean the medical device leads to biofilm formation and bacterial colonization, which may harbor bacterial residuals such as endotoxins.
Endotoxin contamination and its effects on biocompatibility have not yet entered into widespread consciousness among biomaterial specialists. Endotoxins, also called lipopolysacharides (LPS), are an integral part of the outer cell membrane of Gram-negative bacteria that are shed upon cell death, growth, and division. When introduced to the blood stream, they elicit an immune response, especially through monocytes and macrophages. These cells release mediators, such as tumor necrosis factor and free radicals, having potent biological activity responsible for adverse effects. Among these are affecting structure and function of organ cells, changing metabolic functions, raising body temperature (pyrogen reactions) triggering the coagulation cascade, modifying hemodynamics, causing septic shock, and in extreme cases multiple organ failure, with a high mortality rate.
Due to their ubiquitous nature, endotoxins are persistent bio-contaminants that deposit and adhere to many materials. Previous studies have revealed that significant levels (15 endotoxin units (EU)/m2 of surface area) of adherent endotoxin existed on cleaned, passivated, and gamma-sterilized implant surfaces, especially on those made from titanium (Ti). Their ability to adhere to materials has been related to many factors such as material type, surface properties, and pH. However, affinity for metallic biomaterials such as Ti appears to be primarily a function of surface energy. The surface energy of the endotoxins is thought to be about 30 mJ/m2 or less. Hence, for endotoxins to adhere, the biomaterial must exhibit surface energies greater than 30 mJ/m2.
Eliminating endotoxins has been a major challenge to the pharmaceutical and medical industry, and is by far the greatest concern in achieving depyrogenation of medical devices. Yet, a generally applicable method for the removal of endotoxins is not available. Since endotoxins are highly heat-stable they are not destroyed by standard autoclaving conditions. However, endotoxins can be destroyed by dry heat at 250° C. for more than 30 min or at 180° C. for more than 3 h. However, there are possible complications associated with dry-heat decontamination. One is the lack of uniformity of temperature within the oven. Hot air has a tendency to stratify and may not uniformly heat a cooler material. Another complication is heat damage and oxidation of biomaterials. To remove endotoxin from metallic particles a cycle of alkali ethanol (0.1 M NaOH in 95% ethanol) at 30° C. followed by 25% nitric acid both for 18-20 h each is recommended. In reusable medical devices, a useful recommendation to minimize endotoxin contamination is to process, package, and promptly sterilize the item in order to limit the time of bacterial contamination and growth. However, conventional sterilization by steam or ethylene oxide does not destroy endotoxin, and does not alter the pyrogenic activity of endotoxic fragments.
Thus, a need still remains for techniques and processes to achieve safe endotoxin levels on medical devices (e.g., ≦20 EU/device according to the US Pharmacopeia-Standard USP27-NF22).